Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism
We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q1...
Gespeichert in:
| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2011-06, Vol.70 (5), p.863-885 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 885 |
|---|---|
| container_issue | 5 |
| container_start_page | 863 |
| container_title | Neuron (Cambridge, Mass.) |
| container_volume | 70 |
| creator | Sanders, Stephan J. Ercan-Sencicek, A. Gulhan Hus, Vanessa Luo, Rui Murtha, Michael T. Moreno-De-Luca, Daniel Chu, Su H. Moreau, Michael P. Gupta, Abha R. Thomson, Susanne A. Mason, Christopher E. Bilguvar, Kaya Celestino-Soper, Patricia B.S. Choi, Murim Crawford, Emily L. Davis, Lea Davis Wright, Nicole R. Dhodapkar, Rahul M. DiCola, Michael DiLullo, Nicholas M. Fernandez, Thomas V. Fielding-Singh, Vikram Fishman, Daniel O. Frahm, Stephanie Garagaloyan, Rouben Goh, Gerald S. Kammela, Sindhuja Klei, Lambertus Lowe, Jennifer K. Lund, Sabata C. McGrew, Anna D. Meyer, Kyle A. Moffat, William J. Murdoch, John D. O'Roak, Brian J. Ober, Gordon T. Pottenger, Rebecca S. Raubeson, Melanie J. Song, Youeun Wang, Qi Yaspan, Brian L. Yu, Timothy W. Yurkiewicz, Ilana R. Beaudet, Arthur L. Cantor, Rita M. Curland, Martin Grice, Dorothy E. Günel, Murat Lifton, Richard P. Mane, Shrikant M. Martin, Donna M. Shaw, Chad A. Sheldon, Michael Tischfield, Jay A. Walsh, Christopher A. Morrow, Eric M. Ledbetter, David H. Fombonne, Eric Lord, Catherine Martin, Christa Lese Brooks, Andrew I. Sutcliffe, James S. Cook, Edwin H. Geschwind, Daniel Roeder, Kathryn Devlin, Bernie State, Matthew W. |
| description | We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.
► Association of duplications of the Williams syndrome region, 7q11.23 ► Replication of findings of increased de novo CNVs in autism spectrum disorders ► Strong association with ASD at 7q11.23, 15q11.2-13, 16p11.2, and NRXN1 ► Prediction of 130–234 ASD-related de novo CNV regions |
| doi_str_mv | 10.1016/j.neuron.2011.05.002 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_874185514</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0896627311003746</els_id><sourcerecordid>874185514</sourcerecordid><originalsourceid>FETCH-LOGICAL-c467t-3c77ceda2f8bf0eb10312d34131f1565b6772259629b7c521c7ccab198bd084d3</originalsourceid><addsrcrecordid>eNp9kUtv1DAURi0EokPhHyBkiUU3zeBrx3ayQRpNeVQqRaI8llbiOFOPHHtqO0Wz54fj0RQWLFjdzbnffRyEXgJZAgHxZrv0Zo7BLykBWBK-JIQ-QgsgraxqaNvHaEGaVlSCSnaCnqW0JQRq3sJTdEJB8IY3sEC_Ps0u250z-IvRc4zGZ3xh8HW4D3h9_T2d40uv3TxYv8EX885Z3WUbfMJhxPnWYHlXhlOGf1jnbDclfLP3QwzTIW9TwHO8igbf5LLoxu3xKqWgbZfNgH_afItXc7Zpeo6ejJ1L5sVDPUXf3r_7uv5YXX3-cLleXVW6FjJXTEupzdDRselHYnogDOjAamAwAhe8F1JSyltB215qTkFLrbse2qYfSFMP7BSdHXN3MdzNJmU12aSNc503YU6qkTU0nENdyNf_kNswR1-WUyBY3UjOBCtUfaR0DClFM6pdtFMX9wqIOkhSW3WUpA6SFOGqSCptrx7C534yw9-mP1YK8PYImPKMe2uiStoaX2630eishmD_P-E3Anmj_w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1634875363</pqid></control><display><type>article</type><title>Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism</title><source>MEDLINE</source><source>Open Access: Cell Press Free Archives</source><source>Elsevier ScienceDirect Journals</source><source>EZB Electronic Journals Library</source><creator>Sanders, Stephan J. ; Ercan-Sencicek, A. Gulhan ; Hus, Vanessa ; Luo, Rui ; Murtha, Michael T. ; Moreno-De-Luca, Daniel ; Chu, Su H. ; Moreau, Michael P. ; Gupta, Abha R. ; Thomson, Susanne A. ; Mason, Christopher E. ; Bilguvar, Kaya ; Celestino-Soper, Patricia B.S. ; Choi, Murim ; Crawford, Emily L. ; Davis, Lea ; Davis Wright, Nicole R. ; Dhodapkar, Rahul M. ; DiCola, Michael ; DiLullo, Nicholas M. ; Fernandez, Thomas V. ; Fielding-Singh, Vikram ; Fishman, Daniel O. ; Frahm, Stephanie ; Garagaloyan, Rouben ; Goh, Gerald S. ; Kammela, Sindhuja ; Klei, Lambertus ; Lowe, Jennifer K. ; Lund, Sabata C. ; McGrew, Anna D. ; Meyer, Kyle A. ; Moffat, William J. ; Murdoch, John D. ; O'Roak, Brian J. ; Ober, Gordon T. ; Pottenger, Rebecca S. ; Raubeson, Melanie J. ; Song, Youeun ; Wang, Qi ; Yaspan, Brian L. ; Yu, Timothy W. ; Yurkiewicz, Ilana R. ; Beaudet, Arthur L. ; Cantor, Rita M. ; Curland, Martin ; Grice, Dorothy E. ; Günel, Murat ; Lifton, Richard P. ; Mane, Shrikant M. ; Martin, Donna M. ; Shaw, Chad A. ; Sheldon, Michael ; Tischfield, Jay A. ; Walsh, Christopher A. ; Morrow, Eric M. ; Ledbetter, David H. ; Fombonne, Eric ; Lord, Catherine ; Martin, Christa Lese ; Brooks, Andrew I. ; Sutcliffe, James S. ; Cook, Edwin H. ; Geschwind, Daniel ; Roeder, Kathryn ; Devlin, Bernie ; State, Matthew W.</creator><creatorcontrib>Sanders, Stephan J. ; Ercan-Sencicek, A. Gulhan ; Hus, Vanessa ; Luo, Rui ; Murtha, Michael T. ; Moreno-De-Luca, Daniel ; Chu, Su H. ; Moreau, Michael P. ; Gupta, Abha R. ; Thomson, Susanne A. ; Mason, Christopher E. ; Bilguvar, Kaya ; Celestino-Soper, Patricia B.S. ; Choi, Murim ; Crawford, Emily L. ; Davis, Lea ; Davis Wright, Nicole R. ; Dhodapkar, Rahul M. ; DiCola, Michael ; DiLullo, Nicholas M. ; Fernandez, Thomas V. ; Fielding-Singh, Vikram ; Fishman, Daniel O. ; Frahm, Stephanie ; Garagaloyan, Rouben ; Goh, Gerald S. ; Kammela, Sindhuja ; Klei, Lambertus ; Lowe, Jennifer K. ; Lund, Sabata C. ; McGrew, Anna D. ; Meyer, Kyle A. ; Moffat, William J. ; Murdoch, John D. ; O'Roak, Brian J. ; Ober, Gordon T. ; Pottenger, Rebecca S. ; Raubeson, Melanie J. ; Song, Youeun ; Wang, Qi ; Yaspan, Brian L. ; Yu, Timothy W. ; Yurkiewicz, Ilana R. ; Beaudet, Arthur L. ; Cantor, Rita M. ; Curland, Martin ; Grice, Dorothy E. ; Günel, Murat ; Lifton, Richard P. ; Mane, Shrikant M. ; Martin, Donna M. ; Shaw, Chad A. ; Sheldon, Michael ; Tischfield, Jay A. ; Walsh, Christopher A. ; Morrow, Eric M. ; Ledbetter, David H. ; Fombonne, Eric ; Lord, Catherine ; Martin, Christa Lese ; Brooks, Andrew I. ; Sutcliffe, James S. ; Cook, Edwin H. ; Geschwind, Daniel ; Roeder, Kathryn ; Devlin, Bernie ; State, Matthew W.</creatorcontrib><description>We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.
► Association of duplications of the Williams syndrome region, 7q11.23 ► Replication of findings of increased de novo CNVs in autism spectrum disorders ► Strong association with ASD at 7q11.23, 15q11.2-13, 16p11.2, and NRXN1 ► Prediction of 130–234 ASD-related de novo CNV regions</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/j.neuron.2011.05.002</identifier><identifier>PMID: 21658581</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Autism ; Cadherins - genetics ; Calcium-Binding Proteins ; Cell Adhesion Molecules, Neuronal - genetics ; Child ; Child Development Disorders, Pervasive - genetics ; Child, Preschool ; Chromosomes, Human, Pair 16 - genetics ; Chromosomes, Human, Pair 7 - genetics ; Chromosomes, Human, X - genetics ; Design ; DNA Copy Number Variations - genetics ; Family Health ; Female ; Gene Duplication - genetics ; Gene Expression Profiling ; Genome-Wide Association Study ; Genomes ; Genotype ; Humans ; Male ; Mutation ; Nerve Tissue Proteins - genetics ; Neural Cell Adhesion Molecules ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Proteins - genetics ; Siblings ; Studies ; Ubiquitin Thiolesterase - genetics ; Ubiquitin-Specific Peptidase 7 ; Williams Syndrome - genetics</subject><ispartof>Neuron (Cambridge, Mass.), 2011-06, Vol.70 (5), p.863-885</ispartof><rights>2011 Elsevier Inc.</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Jun 9, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-3c77ceda2f8bf0eb10312d34131f1565b6772259629b7c521c7ccab198bd084d3</citedby><cites>FETCH-LOGICAL-c467t-3c77ceda2f8bf0eb10312d34131f1565b6772259629b7c521c7ccab198bd084d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0896627311003746$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21658581$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sanders, Stephan J.</creatorcontrib><creatorcontrib>Ercan-Sencicek, A. Gulhan</creatorcontrib><creatorcontrib>Hus, Vanessa</creatorcontrib><creatorcontrib>Luo, Rui</creatorcontrib><creatorcontrib>Murtha, Michael T.</creatorcontrib><creatorcontrib>Moreno-De-Luca, Daniel</creatorcontrib><creatorcontrib>Chu, Su H.</creatorcontrib><creatorcontrib>Moreau, Michael P.</creatorcontrib><creatorcontrib>Gupta, Abha R.</creatorcontrib><creatorcontrib>Thomson, Susanne A.</creatorcontrib><creatorcontrib>Mason, Christopher E.</creatorcontrib><creatorcontrib>Bilguvar, Kaya</creatorcontrib><creatorcontrib>Celestino-Soper, Patricia B.S.</creatorcontrib><creatorcontrib>Choi, Murim</creatorcontrib><creatorcontrib>Crawford, Emily L.</creatorcontrib><creatorcontrib>Davis, Lea</creatorcontrib><creatorcontrib>Davis Wright, Nicole R.</creatorcontrib><creatorcontrib>Dhodapkar, Rahul M.</creatorcontrib><creatorcontrib>DiCola, Michael</creatorcontrib><creatorcontrib>DiLullo, Nicholas M.</creatorcontrib><creatorcontrib>Fernandez, Thomas V.</creatorcontrib><creatorcontrib>Fielding-Singh, Vikram</creatorcontrib><creatorcontrib>Fishman, Daniel O.</creatorcontrib><creatorcontrib>Frahm, Stephanie</creatorcontrib><creatorcontrib>Garagaloyan, Rouben</creatorcontrib><creatorcontrib>Goh, Gerald S.</creatorcontrib><creatorcontrib>Kammela, Sindhuja</creatorcontrib><creatorcontrib>Klei, Lambertus</creatorcontrib><creatorcontrib>Lowe, Jennifer K.</creatorcontrib><creatorcontrib>Lund, Sabata C.</creatorcontrib><creatorcontrib>McGrew, Anna D.</creatorcontrib><creatorcontrib>Meyer, Kyle A.</creatorcontrib><creatorcontrib>Moffat, William J.</creatorcontrib><creatorcontrib>Murdoch, John D.</creatorcontrib><creatorcontrib>O'Roak, Brian J.</creatorcontrib><creatorcontrib>Ober, Gordon T.</creatorcontrib><creatorcontrib>Pottenger, Rebecca S.</creatorcontrib><creatorcontrib>Raubeson, Melanie J.</creatorcontrib><creatorcontrib>Song, Youeun</creatorcontrib><creatorcontrib>Wang, Qi</creatorcontrib><creatorcontrib>Yaspan, Brian L.</creatorcontrib><creatorcontrib>Yu, Timothy W.</creatorcontrib><creatorcontrib>Yurkiewicz, Ilana R.</creatorcontrib><creatorcontrib>Beaudet, Arthur L.</creatorcontrib><creatorcontrib>Cantor, Rita M.</creatorcontrib><creatorcontrib>Curland, Martin</creatorcontrib><creatorcontrib>Grice, Dorothy E.</creatorcontrib><creatorcontrib>Günel, Murat</creatorcontrib><creatorcontrib>Lifton, Richard P.</creatorcontrib><creatorcontrib>Mane, Shrikant M.</creatorcontrib><creatorcontrib>Martin, Donna M.</creatorcontrib><creatorcontrib>Shaw, Chad A.</creatorcontrib><creatorcontrib>Sheldon, Michael</creatorcontrib><creatorcontrib>Tischfield, Jay A.</creatorcontrib><creatorcontrib>Walsh, Christopher A.</creatorcontrib><creatorcontrib>Morrow, Eric M.</creatorcontrib><creatorcontrib>Ledbetter, David H.</creatorcontrib><creatorcontrib>Fombonne, Eric</creatorcontrib><creatorcontrib>Lord, Catherine</creatorcontrib><creatorcontrib>Martin, Christa Lese</creatorcontrib><creatorcontrib>Brooks, Andrew I.</creatorcontrib><creatorcontrib>Sutcliffe, James S.</creatorcontrib><creatorcontrib>Cook, Edwin H.</creatorcontrib><creatorcontrib>Geschwind, Daniel</creatorcontrib><creatorcontrib>Roeder, Kathryn</creatorcontrib><creatorcontrib>Devlin, Bernie</creatorcontrib><creatorcontrib>State, Matthew W.</creatorcontrib><title>Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.
► Association of duplications of the Williams syndrome region, 7q11.23 ► Replication of findings of increased de novo CNVs in autism spectrum disorders ► Strong association with ASD at 7q11.23, 15q11.2-13, 16p11.2, and NRXN1 ► Prediction of 130–234 ASD-related de novo CNV regions</description><subject>Adolescent</subject><subject>Autism</subject><subject>Cadherins - genetics</subject><subject>Calcium-Binding Proteins</subject><subject>Cell Adhesion Molecules, Neuronal - genetics</subject><subject>Child</subject><subject>Child Development Disorders, Pervasive - genetics</subject><subject>Child, Preschool</subject><subject>Chromosomes, Human, Pair 16 - genetics</subject><subject>Chromosomes, Human, Pair 7 - genetics</subject><subject>Chromosomes, Human, X - genetics</subject><subject>Design</subject><subject>DNA Copy Number Variations - genetics</subject><subject>Family Health</subject><subject>Female</subject><subject>Gene Duplication - genetics</subject><subject>Gene Expression Profiling</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Humans</subject><subject>Male</subject><subject>Mutation</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Neural Cell Adhesion Molecules</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Phenotype</subject><subject>Proteins - genetics</subject><subject>Siblings</subject><subject>Studies</subject><subject>Ubiquitin Thiolesterase - genetics</subject><subject>Ubiquitin-Specific Peptidase 7</subject><subject>Williams Syndrome - genetics</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtv1DAURi0EokPhHyBkiUU3zeBrx3ayQRpNeVQqRaI8llbiOFOPHHtqO0Wz54fj0RQWLFjdzbnffRyEXgJZAgHxZrv0Zo7BLykBWBK-JIQ-QgsgraxqaNvHaEGaVlSCSnaCnqW0JQRq3sJTdEJB8IY3sEC_Ps0u250z-IvRc4zGZ3xh8HW4D3h9_T2d40uv3TxYv8EX885Z3WUbfMJhxPnWYHlXhlOGf1jnbDclfLP3QwzTIW9TwHO8igbf5LLoxu3xKqWgbZfNgH_afItXc7Zpeo6ejJ1L5sVDPUXf3r_7uv5YXX3-cLleXVW6FjJXTEupzdDRselHYnogDOjAamAwAhe8F1JSyltB215qTkFLrbse2qYfSFMP7BSdHXN3MdzNJmU12aSNc503YU6qkTU0nENdyNf_kNswR1-WUyBY3UjOBCtUfaR0DClFM6pdtFMX9wqIOkhSW3WUpA6SFOGqSCptrx7C534yw9-mP1YK8PYImPKMe2uiStoaX2630eishmD_P-E3Anmj_w</recordid><startdate>20110609</startdate><enddate>20110609</enddate><creator>Sanders, Stephan J.</creator><creator>Ercan-Sencicek, A. Gulhan</creator><creator>Hus, Vanessa</creator><creator>Luo, Rui</creator><creator>Murtha, Michael T.</creator><creator>Moreno-De-Luca, Daniel</creator><creator>Chu, Su H.</creator><creator>Moreau, Michael P.</creator><creator>Gupta, Abha R.</creator><creator>Thomson, Susanne A.</creator><creator>Mason, Christopher E.</creator><creator>Bilguvar, Kaya</creator><creator>Celestino-Soper, Patricia B.S.</creator><creator>Choi, Murim</creator><creator>Crawford, Emily L.</creator><creator>Davis, Lea</creator><creator>Davis Wright, Nicole R.</creator><creator>Dhodapkar, Rahul M.</creator><creator>DiCola, Michael</creator><creator>DiLullo, Nicholas M.</creator><creator>Fernandez, Thomas V.</creator><creator>Fielding-Singh, Vikram</creator><creator>Fishman, Daniel O.</creator><creator>Frahm, Stephanie</creator><creator>Garagaloyan, Rouben</creator><creator>Goh, Gerald S.</creator><creator>Kammela, Sindhuja</creator><creator>Klei, Lambertus</creator><creator>Lowe, Jennifer K.</creator><creator>Lund, Sabata C.</creator><creator>McGrew, Anna D.</creator><creator>Meyer, Kyle A.</creator><creator>Moffat, William J.</creator><creator>Murdoch, John D.</creator><creator>O'Roak, Brian J.</creator><creator>Ober, Gordon T.</creator><creator>Pottenger, Rebecca S.</creator><creator>Raubeson, Melanie J.</creator><creator>Song, Youeun</creator><creator>Wang, Qi</creator><creator>Yaspan, Brian L.</creator><creator>Yu, Timothy W.</creator><creator>Yurkiewicz, Ilana R.</creator><creator>Beaudet, Arthur L.</creator><creator>Cantor, Rita M.</creator><creator>Curland, Martin</creator><creator>Grice, Dorothy E.</creator><creator>Günel, Murat</creator><creator>Lifton, Richard P.</creator><creator>Mane, Shrikant M.</creator><creator>Martin, Donna M.</creator><creator>Shaw, Chad A.</creator><creator>Sheldon, Michael</creator><creator>Tischfield, Jay A.</creator><creator>Walsh, Christopher A.</creator><creator>Morrow, Eric M.</creator><creator>Ledbetter, David H.</creator><creator>Fombonne, Eric</creator><creator>Lord, Catherine</creator><creator>Martin, Christa Lese</creator><creator>Brooks, Andrew I.</creator><creator>Sutcliffe, James S.</creator><creator>Cook, Edwin H.</creator><creator>Geschwind, Daniel</creator><creator>Roeder, Kathryn</creator><creator>Devlin, Bernie</creator><creator>State, Matthew W.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20110609</creationdate><title>Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism</title><author>Sanders, Stephan J. ; Ercan-Sencicek, A. Gulhan ; Hus, Vanessa ; Luo, Rui ; Murtha, Michael T. ; Moreno-De-Luca, Daniel ; Chu, Su H. ; Moreau, Michael P. ; Gupta, Abha R. ; Thomson, Susanne A. ; Mason, Christopher E. ; Bilguvar, Kaya ; Celestino-Soper, Patricia B.S. ; Choi, Murim ; Crawford, Emily L. ; Davis, Lea ; Davis Wright, Nicole R. ; Dhodapkar, Rahul M. ; DiCola, Michael ; DiLullo, Nicholas M. ; Fernandez, Thomas V. ; Fielding-Singh, Vikram ; Fishman, Daniel O. ; Frahm, Stephanie ; Garagaloyan, Rouben ; Goh, Gerald S. ; Kammela, Sindhuja ; Klei, Lambertus ; Lowe, Jennifer K. ; Lund, Sabata C. ; McGrew, Anna D. ; Meyer, Kyle A. ; Moffat, William J. ; Murdoch, John D. ; O'Roak, Brian J. ; Ober, Gordon T. ; Pottenger, Rebecca S. ; Raubeson, Melanie J. ; Song, Youeun ; Wang, Qi ; Yaspan, Brian L. ; Yu, Timothy W. ; Yurkiewicz, Ilana R. ; Beaudet, Arthur L. ; Cantor, Rita M. ; Curland, Martin ; Grice, Dorothy E. ; Günel, Murat ; Lifton, Richard P. ; Mane, Shrikant M. ; Martin, Donna M. ; Shaw, Chad A. ; Sheldon, Michael ; Tischfield, Jay A. ; Walsh, Christopher A. ; Morrow, Eric M. ; Ledbetter, David H. ; Fombonne, Eric ; Lord, Catherine ; Martin, Christa Lese ; Brooks, Andrew I. ; Sutcliffe, James S. ; Cook, Edwin H. ; Geschwind, Daniel ; Roeder, Kathryn ; Devlin, Bernie ; State, Matthew W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-3c77ceda2f8bf0eb10312d34131f1565b6772259629b7c521c7ccab198bd084d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adolescent</topic><topic>Autism</topic><topic>Cadherins - genetics</topic><topic>Calcium-Binding Proteins</topic><topic>Cell Adhesion Molecules, Neuronal - genetics</topic><topic>Child</topic><topic>Child Development Disorders, Pervasive - genetics</topic><topic>Child, Preschool</topic><topic>Chromosomes, Human, Pair 16 - genetics</topic><topic>Chromosomes, Human, Pair 7 - genetics</topic><topic>Chromosomes, Human, X - genetics</topic><topic>Design</topic><topic>DNA Copy Number Variations - genetics</topic><topic>Family Health</topic><topic>Female</topic><topic>Gene Duplication - genetics</topic><topic>Gene Expression Profiling</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Humans</topic><topic>Male</topic><topic>Mutation</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Neural Cell Adhesion Molecules</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Phenotype</topic><topic>Proteins - genetics</topic><topic>Siblings</topic><topic>Studies</topic><topic>Ubiquitin Thiolesterase - genetics</topic><topic>Ubiquitin-Specific Peptidase 7</topic><topic>Williams Syndrome - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sanders, Stephan J.</creatorcontrib><creatorcontrib>Ercan-Sencicek, A. Gulhan</creatorcontrib><creatorcontrib>Hus, Vanessa</creatorcontrib><creatorcontrib>Luo, Rui</creatorcontrib><creatorcontrib>Murtha, Michael T.</creatorcontrib><creatorcontrib>Moreno-De-Luca, Daniel</creatorcontrib><creatorcontrib>Chu, Su H.</creatorcontrib><creatorcontrib>Moreau, Michael P.</creatorcontrib><creatorcontrib>Gupta, Abha R.</creatorcontrib><creatorcontrib>Thomson, Susanne A.</creatorcontrib><creatorcontrib>Mason, Christopher E.</creatorcontrib><creatorcontrib>Bilguvar, Kaya</creatorcontrib><creatorcontrib>Celestino-Soper, Patricia B.S.</creatorcontrib><creatorcontrib>Choi, Murim</creatorcontrib><creatorcontrib>Crawford, Emily L.</creatorcontrib><creatorcontrib>Davis, Lea</creatorcontrib><creatorcontrib>Davis Wright, Nicole R.</creatorcontrib><creatorcontrib>Dhodapkar, Rahul M.</creatorcontrib><creatorcontrib>DiCola, Michael</creatorcontrib><creatorcontrib>DiLullo, Nicholas M.</creatorcontrib><creatorcontrib>Fernandez, Thomas V.</creatorcontrib><creatorcontrib>Fielding-Singh, Vikram</creatorcontrib><creatorcontrib>Fishman, Daniel O.</creatorcontrib><creatorcontrib>Frahm, Stephanie</creatorcontrib><creatorcontrib>Garagaloyan, Rouben</creatorcontrib><creatorcontrib>Goh, Gerald S.</creatorcontrib><creatorcontrib>Kammela, Sindhuja</creatorcontrib><creatorcontrib>Klei, Lambertus</creatorcontrib><creatorcontrib>Lowe, Jennifer K.</creatorcontrib><creatorcontrib>Lund, Sabata C.</creatorcontrib><creatorcontrib>McGrew, Anna D.</creatorcontrib><creatorcontrib>Meyer, Kyle A.</creatorcontrib><creatorcontrib>Moffat, William J.</creatorcontrib><creatorcontrib>Murdoch, John D.</creatorcontrib><creatorcontrib>O'Roak, Brian J.</creatorcontrib><creatorcontrib>Ober, Gordon T.</creatorcontrib><creatorcontrib>Pottenger, Rebecca S.</creatorcontrib><creatorcontrib>Raubeson, Melanie J.</creatorcontrib><creatorcontrib>Song, Youeun</creatorcontrib><creatorcontrib>Wang, Qi</creatorcontrib><creatorcontrib>Yaspan, Brian L.</creatorcontrib><creatorcontrib>Yu, Timothy W.</creatorcontrib><creatorcontrib>Yurkiewicz, Ilana R.</creatorcontrib><creatorcontrib>Beaudet, Arthur L.</creatorcontrib><creatorcontrib>Cantor, Rita M.</creatorcontrib><creatorcontrib>Curland, Martin</creatorcontrib><creatorcontrib>Grice, Dorothy E.</creatorcontrib><creatorcontrib>Günel, Murat</creatorcontrib><creatorcontrib>Lifton, Richard P.</creatorcontrib><creatorcontrib>Mane, Shrikant M.</creatorcontrib><creatorcontrib>Martin, Donna M.</creatorcontrib><creatorcontrib>Shaw, Chad A.</creatorcontrib><creatorcontrib>Sheldon, Michael</creatorcontrib><creatorcontrib>Tischfield, Jay A.</creatorcontrib><creatorcontrib>Walsh, Christopher A.</creatorcontrib><creatorcontrib>Morrow, Eric M.</creatorcontrib><creatorcontrib>Ledbetter, David H.</creatorcontrib><creatorcontrib>Fombonne, Eric</creatorcontrib><creatorcontrib>Lord, Catherine</creatorcontrib><creatorcontrib>Martin, Christa Lese</creatorcontrib><creatorcontrib>Brooks, Andrew I.</creatorcontrib><creatorcontrib>Sutcliffe, James S.</creatorcontrib><creatorcontrib>Cook, Edwin H.</creatorcontrib><creatorcontrib>Geschwind, Daniel</creatorcontrib><creatorcontrib>Roeder, Kathryn</creatorcontrib><creatorcontrib>Devlin, Bernie</creatorcontrib><creatorcontrib>State, Matthew W.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sanders, Stephan J.</au><au>Ercan-Sencicek, A. Gulhan</au><au>Hus, Vanessa</au><au>Luo, Rui</au><au>Murtha, Michael T.</au><au>Moreno-De-Luca, Daniel</au><au>Chu, Su H.</au><au>Moreau, Michael P.</au><au>Gupta, Abha R.</au><au>Thomson, Susanne A.</au><au>Mason, Christopher E.</au><au>Bilguvar, Kaya</au><au>Celestino-Soper, Patricia B.S.</au><au>Choi, Murim</au><au>Crawford, Emily L.</au><au>Davis, Lea</au><au>Davis Wright, Nicole R.</au><au>Dhodapkar, Rahul M.</au><au>DiCola, Michael</au><au>DiLullo, Nicholas M.</au><au>Fernandez, Thomas V.</au><au>Fielding-Singh, Vikram</au><au>Fishman, Daniel O.</au><au>Frahm, Stephanie</au><au>Garagaloyan, Rouben</au><au>Goh, Gerald S.</au><au>Kammela, Sindhuja</au><au>Klei, Lambertus</au><au>Lowe, Jennifer K.</au><au>Lund, Sabata C.</au><au>McGrew, Anna D.</au><au>Meyer, Kyle A.</au><au>Moffat, William J.</au><au>Murdoch, John D.</au><au>O'Roak, Brian J.</au><au>Ober, Gordon T.</au><au>Pottenger, Rebecca S.</au><au>Raubeson, Melanie J.</au><au>Song, Youeun</au><au>Wang, Qi</au><au>Yaspan, Brian L.</au><au>Yu, Timothy W.</au><au>Yurkiewicz, Ilana R.</au><au>Beaudet, Arthur L.</au><au>Cantor, Rita M.</au><au>Curland, Martin</au><au>Grice, Dorothy E.</au><au>Günel, Murat</au><au>Lifton, Richard P.</au><au>Mane, Shrikant M.</au><au>Martin, Donna M.</au><au>Shaw, Chad A.</au><au>Sheldon, Michael</au><au>Tischfield, Jay A.</au><au>Walsh, Christopher A.</au><au>Morrow, Eric M.</au><au>Ledbetter, David H.</au><au>Fombonne, Eric</au><au>Lord, Catherine</au><au>Martin, Christa Lese</au><au>Brooks, Andrew I.</au><au>Sutcliffe, James S.</au><au>Cook, Edwin H.</au><au>Geschwind, Daniel</au><au>Roeder, Kathryn</au><au>Devlin, Bernie</au><au>State, Matthew W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>2011-06-09</date><risdate>2011</risdate><volume>70</volume><issue>5</issue><spage>863</spage><epage>885</epage><pages>863-885</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><abstract>We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.
► Association of duplications of the Williams syndrome region, 7q11.23 ► Replication of findings of increased de novo CNVs in autism spectrum disorders ► Strong association with ASD at 7q11.23, 15q11.2-13, 16p11.2, and NRXN1 ► Prediction of 130–234 ASD-related de novo CNV regions</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21658581</pmid><doi>10.1016/j.neuron.2011.05.002</doi><tpages>23</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0896-6273 |
| ispartof | Neuron (Cambridge, Mass.), 2011-06, Vol.70 (5), p.863-885 |
| issn | 0896-6273 1097-4199 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_874185514 |
| source | MEDLINE; Open Access: Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB Electronic Journals Library |
| subjects | Adolescent Autism Cadherins - genetics Calcium-Binding Proteins Cell Adhesion Molecules, Neuronal - genetics Child Child Development Disorders, Pervasive - genetics Child, Preschool Chromosomes, Human, Pair 16 - genetics Chromosomes, Human, Pair 7 - genetics Chromosomes, Human, X - genetics Design DNA Copy Number Variations - genetics Family Health Female Gene Duplication - genetics Gene Expression Profiling Genome-Wide Association Study Genomes Genotype Humans Male Mutation Nerve Tissue Proteins - genetics Neural Cell Adhesion Molecules Oligonucleotide Array Sequence Analysis Phenotype Proteins - genetics Siblings Studies Ubiquitin Thiolesterase - genetics Ubiquitin-Specific Peptidase 7 Williams Syndrome - genetics |
| title | Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T19%3A00%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multiple%20Recurrent%20De%20Novo%20CNVs,%20Including%20Duplications%20of%20the%207q11.23%20Williams%20Syndrome%20Region,%20Are%20Strongly%20Associated%20with%20Autism&rft.jtitle=Neuron%20(Cambridge,%20Mass.)&rft.au=Sanders,%20Stephan%C2%A0J.&rft.date=2011-06-09&rft.volume=70&rft.issue=5&rft.spage=863&rft.epage=885&rft.pages=863-885&rft.issn=0896-6273&rft.eissn=1097-4199&rft_id=info:doi/10.1016/j.neuron.2011.05.002&rft_dat=%3Cproquest_cross%3E874185514%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1634875363&rft_id=info:pmid/21658581&rft_els_id=S0896627311003746&rfr_iscdi=true |